In this study of drug-resistant E. coli bacteriuria spanning more than 6 years in a safety-net public healthcare system serving a diverse population, we found antimicrobial resistant E. coli frequency to increase over time in both community and healthcare settings. The magnitude of the increase was greatest among ESBL-E. coli bacteriuria, which doubled in community settings and increased by more than 40% in healthcare settings. Older age, male sex, and Chinese dialect or Spanish as a preferred language (or, in some models, Latinx race/ethnicity) were associated with higher prevalence of ESBL-E. coli among all E. coli bacteriuria episodes.
Increasing prevalence of ESBL-E. coli in community-onset and healthcare onset/associated infections is now observed worldwide.[4, 10, 12, 18–22] A 2019 CDC report showed a 50% increase in hospital- and community-onset infections caused by ESBL-producing Enterobacteriaceae between 2012 and 2017 in the US.[2] A report from the Study for Monitoring Antimicrobial Resistance Trends (SMART) found prevalence of urinary tract infections caused by ESBL-E. coli to increase from 7.8–18.3% between 2010 and 2014 in the US, particularly among hospital-associated infections.[23] In contrast, the authors found increasing prevalence in community-onset infections in Canada.[23] Most recently, a report on urinary tract infections in US hospitalized patients found a prevalence of 17.2% for ESBL-producing Enterobacteriaceae.[24] We have previously shown increase in ESBL-E. coli bacteriuria cases in the same San Francisco public healthcare system, but were unable to decipher whether this increase occurred in community or healthcare settings.[15] Here, while prevalence and increase per year was greater in healthcare onset/associated ESBL-E. coli bacteriuria, we also found a significant increase among community-onset bacteriuria.
We first compared ESBL-E. coli bacteriuria to bacteriuria caused by all other E. coli strains (non-ESBL drug-resistant and drug-susceptible E. coli), which would not necessarily distinguish risk factors associated with ESBL-E. coli from those associated with drug-resistant E. coli. Therefore, we performed secondary analyses comparing ESBL-E. coli bacteriuria to bacteriuria caused by non-ESBL drug-resistant E. coli. For community-onset ESBL-E. coli bacteriuria, we found older age and male gender to be associated risk factors. For healthcare-onset/associated bacteriuria, we found male gender to be associated with ESBL-E. coli.
The association with older age and male gender may represent complicated urinary tract infections more likely to occur in these populations, which may include catheter-associated infections or prostatitis requiring prolonged treatment with extended-spectrum beta-lactam drugs.[25] Since multidrug resistance is associated with ESBL-E. coli, factors contributing to frequent antibiotic exposures among older persons in community settings, such as frequent contact with healthcare, higher likelihood of recurrent urinary tract infection, and urinary retention requiring catheterization, may also contribute to the ESBL-E. coli selection.[9, 11, 26–28]
Few studies have found differences in ESBL-E. coli infection by race/ethnicity, independent of healthcare exposures. A New York study found that children identified as Asian had greater odds of infection with ESBL-producing Enterobacteriaceae.[13] Studies utilizing genotyping methods have found that the majority of community-onset urinary tract infection caused by ESBL-E. coli are caused by major pandemic E. coli lineages belonging to specific sequence types, including ST131 and ST69.[9, 10, 29] This may point to common-source exposures in the community. There is mounting evidence that infection with ESBL-E. coli is associated with international travel, particularly to South Asian countries, and food habits, including eating meat contaminated with ESBL-E. coli.[11–14]
No study to our knowledge has found higher risk of ESBL-E. coli in Latinx populations. Our findings may represent increased access to antibiotics by this population in San Francisco, but prior studies from other regions in the US found no difference in access to and use of non-prescribed antibiotics among Latinx compared to non-Latinx individuals.[30] A majority of Latinx patients in this public healthcare system come from Mexico. Travel to Mexico may be a risk factor in our study population. A report from the SMART study showed that Mexico has the highest prevalence of community infections caused by ESBL-E. coli in Latin America.[31] Thus, unmeasured risk factors, such as travel and food consumption, may also be driving increasing community-onset bacteriuria caused by ESBL-E. coli.
While co-resistance of ESBL-E. coli to other antimicrobial agents, specifically fluoroquinolones and trimethoprim-sulfamethoxazole, is very common,[3, 9, 32–34] even more concerning is our finding of phenotypic carbapenem co-resistance amongst ESBL-E. coli. We found that 12 (86%) of 14 carbapenem-resistant E. coli were ESBL-E. coli, although we do not have genetic information to evaluate whether they were carbapenemase-producers. A new report from the CRACKLE2 study found that 20% of non-carbapenemase-producing carbapenem-resistant Enterobacteriales isolated from hospitalized patients produced CTX-M, a common ESBL type.[35]
There are several limitations to our study. First, community-onset cases were defined as cases with no history of hospitalizations in the 90 days at SFGH or LHH prior to urine culture. We did not obtain patient information before 90 days, when such patients could have had other healthcare exposures. Second, it may be that we underestimated hospitalization in the 90 days prior to urine culture if individuals were hospitalized in other healthcare systems. Prior studies, however, have shown high retention rate of patients within our public healthcare system.[36] Lastly, while our study population is diverse in its racial/ethnic representation and their San Francisco neighborhoods, it is homogenous in that individuals receiving care in this public healthcare system have similar socio-economic circumstances. Thus, findings from our study may not be generalizable to other populations.